离子通道与阴茎勃起

近年研究发现某些疾病是离子通道基因缺陷与功能变异的结果 ,称为离子通道病。许多疾病虽然不属于离子通道病 ,但疾病发生的某一环节或阶段与离子通道的功能障碍有着密切的关系 ,而且还发现许多药物防治疾病是通过作用于离子通道起效的。因此 ,生理和疾病与离子通道关系的研究逐渐成为当前研究的热点之一。本文简要综述了近年来离子通道与阴茎勃起关系的研究进展。     

蛋白质组学在弱精子症中的研究进展

男性不育是不孕不育的重要原因之一,这一疾病也严重困扰着患者和医生.据统计,不育症夫妇中50%是男性不育所致,其中,弱精子症占有相当大的比例.研究发现,精子活动能力下降与一氧化氮和超氧化物岐化酶、钙离子通道、微量元素异常以及蛋白质络氨酸磷酸化和膜流动性等很多因素相关.近来,蛋白质组学在弱精子症中的研究日趋兴起.     

Catsper通道蛋白与精子功能

正常生理情况下,精子需要经过超活化获能后才具备使卵子受精的能力,而钙离子内流是精子超活化、获能及顶体反应的关键过程.目前已经发现了许多精子的钙离子通道包括环腺苷通道、电压门控通道、短暂受体潜在通道以及精子特异性表达的钙离子通道-Catsper通道,Catsper通道蛋白家族主要包括:catsper1,catsper2,catsper3和catsper4,他们在精子动力和男性生殖中发挥重要作用,其中任何一个基因受到破坏都会影响精子的运动性能,引起精子超活化失败而导致男性不育.     

环核苷酸门控通道与精子功能

环核苷酸门控通道(CNG)是非选择性阳离子通道,直接由环核苷酸活化,是Ca2+进入细胞内的主要通道之一。CNG通道蛋白由6个不同基因编码,4个A亚单位和2个B亚单位。CNG通道受Ca2+/钙调蛋白和磷酸化/去磷酸化作用所调控。近年来,CNG通道在生殖系统方面的研究受到了广泛关注。大量研究表明,CNG通道在精子运动、获能和顶体反应中起着重要的作用。本文对CNG通道与精子功能的关系进行综述。     

GABA受体调节精子顶体反应和获能的研究进展

GABA受体广泛分布于哺乳动物生殖系统,包括睾丸生精细胞和精子。研究发现GABA受体在受精过程中精子重要生理变化——顶体反应和获能中起着重要调节作用,其可能是体内激素孕酮和透明带诱发顶体反应的作用靶点之一。GABA受体促进顶体反应和获能作刚可能与其调节细胞膜电位从而介导胞膜电压依赖性钙通道开放有关,其机制可能还涉及多种信号通路。本文就目前GABA受体调节精子顶体反应和获能作用的研究现状作一综述。     

GABA受体调节精子顶体反应和口获能的研究进展

GABA受体广泛分布于哺乳动物生殖系统,包括睾丸生精细胞和精子.研究发现GABA受体在受精过程中精子重要生理变化——顶体反应和获能中起着重要调节作用,其可能是体内激素孕酮和透明带诱发顶体反应的作用靶点之一.GABA受体促进顶体反应和获能作用可能与其调节细胞膜电位从而介导胞膜电压依赖性钙通道开放有关,其机制可能还涉及多种信号通路.本文就目前GABA受体调节精子顶体反应和获能作用的研究现状作一综述.     

离子与离子通道在精子获能中的调控机制

哺乳类动物精子膜上的离子通道,包括Ca2+、Na+、K+、Cl-和HCO3-等通道,在精子获能过程中发挥各自重要的作用。精子获能过程通过Ca2+、HCO3-、活性氧等信号分子,激活可溶性腺苷酸环化酶,在环磷酸腺苷(cAMP)、Ca2+以及胞内pH协作下,经cAMP/蛋白激酶A(PKA)和酪氨酸磷酸化信号转导途径促进精子发生获能相关生物效应。     

离子通道在骨关节炎发病机制中的作用研究进展

由于离子通道参与许多细胞过程，作用于离子通道的药物长期以来被用于治疗许多疾病，特别是那些影响组织细胞电兴奋的疾病。随着离子通道病理学机制的不断研究，离子通道已被确定为潜在的新药靶点，许多针对离子通道的基础药物的治疗价值得到了证实。对药物-离子通道相互作用的实验研究表明，离子通道突变可以增加或减少对药物的亲和力，改变其潜在的治疗效果。与可能影响药物药效的通道基因多态性的发现一样，这些发现强调了离子通道研究的必要性，以便识别对通道亚型或突变体有更具体作用的药物，以提高疗效和减少不良反应。随着对离子通道遗传学、结构和功能的更深入理解，以及对新一级和二级离子通道疾病的识别，用于骨关节炎(osteoarthritis, OA)的离子通道药物的数量将大幅增加。笔者就离子通道在OA发病机制中的作用进行了综述，重点介绍了电压门控钠通道Nav1.7、嘌呤类受体P2X3、瞬时感受器电位受体TRPV1、氯离子(Cl^-)通道。从而进一步指导药物研发，以期为OA的诊疗和机制研究提供参考依据。     

钙离子通道在精子运动中的作用及其临床意义

作为一种细胞内重要的信使物质,钙离子在精子运动中发挥着重要作用。钙离子对精子运动的调控主要是通过精子质膜上相关的钙离子通道所介导,其中包括电压门控钙离子通道、环核苷酸门控通道、电压门控阳离子通道和瞬时感受器电位家族,这些通道的任何一个环节出现问题均可以导致精子活动力的下降。本文就近年来与精子运动相关的钙离子通道的研究进展进行了简要综述。     

精子蛋白表达下调在成人弱精症中的意义分析

目的:探讨精子蛋白表达下调在成人弱精症中的意义。方法:用iTRAQ标记以及二维高效液相色谱/串联质谱联用的方法研究成年男性正常精子以及轻、中、重度弱精症患者的精子蛋白表达情况。结果:以正常组作为参照,本研究共发现1 073个蛋白质,其中呈递减下调表达的蛋白质73个,分别是参与精子能量代谢过程蛋白质、参与精子运动和细胞循环途径蛋白质、参与精子细胞免疫反应和凋亡途径蛋白质和其他蛋白质,其中部分蛋白与精子活力明显相关。结论:部分精子蛋白质表达下调可能是导致成人弱精症的重要原因之一。     

Calcium channels — basic aspects of their structure, function and gene encoding; anesthetic action on the channels — a review

PURPOSE: To review recent findings concerning Ca(2+) channel subtype/structure/function from electrophysiological and molecular biological studies and to explain Ca(2+) channel diseases and the actions of anesthetics on Ca(2+) channels. SOURCE: The information was obtained from articles published recently and from our published work. PRINCIPAL FINDINGS: Voltage-dependent Ca(2+) channels serve as one of the important mechanisms for Ca(2+) influx into the cells, enabling the regulation of intracellular concentration of free Ca(2+). Recent advances both in electrophysiology and in molecular biology have made it possible to observe channel activity directly and to investigate channel functions at molecular levels. The Ca(2+) channel can be divided into subtypes according to electrophysiological characteristics, and each subtype has its own gene. The L-type Ca(2+) channel is the target of a large number of clinically important drugs, especially dihydropyridines, and binding sites of Ca(2+) antagonists have been clarified. The effects of various kinds of anesthetics in a variety of cell types have been demonstrated, and some clinical effects of anesthetics can be explained by the effects on Ca(2+) channels. It has recently become apparent that some hereditary diseases such as hypokalemic periodic paralysis result from calcium channelopathies. CONCLUSION: Recent advances both in electrophysiology and in molecular biology have made it possible to clarify the Ca(2+) channel structures, functions, genes, and the anesthetic actions on the channels in detail. The effects of anesthetics on the Ca(2+) channels either of patients with hereditary channelopathies or using gene mutation techniques are left to be discovered.     

Ion channels in sperm physiology and male fertility and infertility

Ion channels regulate the membrane potential and intracellular ionic concentration and thus serve a central role in various cellular processes. Several ion channels have been identified in the germ cells, including sperm, emphasizing their importance in male fertility and reproduction. The molecular mechanism of ion transport and the nature of the ion channels involved have begun to emerge only recently despite the fact that several ligand-gated and voltage-gated channels have been identified and localized on sperm. The presence of the sperm-associated cation channel (CatSper1-4) gene family, proton voltage-gated ion channel (Hv1), potassium voltage-gated ion channel (SLO3/KCNU1), sodium voltage-gated channel (NaV1.1-1.9), and the members of the transient receptor potential (TRP) channel family suggest an indispensable role for ion channels in sperm physiology and fertility potential. Ion channels are the key players in very important processes such as capacitation and the acrosome reaction, which are critical steps in sperm physiology preparing for fertilization. For example, CatSper, Hv1, SLO3, and TRP channel family members have been proposed to participate in the acrosome reaction, thereby making them most important for sperm fertility. Similarly, NaV channels could play a crucial role in noncapacitated sperm and in the initial capacitation steps. The role of ion channels seems indispensable for sperm fertility as evidenced by studies on animal models; however, the functional defects in infertile human males await further exploration. This article represents an update on the role of ion channels in sperm physiology, male fertility, and infertility.     

Calcium channelopathies

Calcium is an important intracellular signaling molecule, and altered calcium channel function can cause widespread cellular changes. Genetic mutations in calcium channels that cause what appear to be trivial alterations of calcium currents in vitro can result in serious diseases in muscles and the nervous system. This article reviews calcium channelopathies in humans and mice.     

离子通道、磷酸化和哺乳动物精子获能

有性生殖动物需要精子和卵子之间进行精心协调的交流才能产生新的个体。精子获能是发生在女性生殖系统中的生殖细胞成熟的一个复杂现象，让精子能够和卵子联结并融合，是哺乳动物生育的必要条件。精子获能过程包括了质膜重组、离子渗透调节、胆固醇减少和许多蛋白质磷酸化状态的变化。研究精子离子通道的新工具能用更好的时空解析度将细胞内的离子变化和蛋白图像化，这些工具正在一步步阐明离子运输和磷酸化状态中的一系列调节是如何引起获能的。最近的证据表明有两条平行的通路调节引起获能的磷酸化发生。其中一条通路要求蛋白激酶A活化，另一条通路需要丝氨酸／苏氨酸磷酸酶失活。本文综述了精子获能所要求的离子运输参与和磷酸化信号处理。理解导致生育的分子机制，对于人们应对男性不育率升高、开发安全的以雄性配子为基础的避孕药、通过辅助生殖策略保持生物多样性都至关重要。     

Ion channels, phosphorylation and mammalian sperm capacitation

Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies.     

Genetic analysis of ion channel dysfunction in Drosophila

To dissect the molecular mechanisms of electrical activity in the nervous system, an extensive collection of mutations affecting various types of voltage-gated ion channels was identified and characterized in Drosophila. Most of these mutations were generated by chemical mutagenesis and were recognized on the basis of defects in motor behavior. These were the first genetically determined ion channelopathies to be characterized in any multicellular organism. Drosophila is a particularly attractive model system for such studies because of the availability of powerful genetic, electrophysiological, and molecular techniques for generating new mutations, characterizing their phenotypes, and cloning the genes thus defined. Consequently, a number of ion channels, including various types of K+ channels that had not yielded previously to biochemical approaches, were first identified via a genetic strategy in Drosophila. Evolutionary conservation of these genes enabled subsequent isolation of the corresponding genes from various mammals, including humans. Several of these human homologues have been found to be associated with heritable neuromuscular disorders. Studies of ion channel mutations in Drosophila have thus provided important biological information concerning the molecular and functional diversity of ion channels, their evolutionary relationships, and their in vivo functions in the nervous system. Similar studies of additional new mutations should now facilitate the analysis of ion channel regulatory mechanisms.